1. Field of the Invention
The present invention relates to an analytical method and device utilizing magnetic materials and acoustics sensor, in particular, an analytical method and device that combines the use of magnetic materials and mass-sensitive sensor.
2. Description of the Related Art
There are in general two approaches to assaying a substance in a sample. One is utilizing separation technique, such as solvent extraction, condensation, precipitation, or chromatography to purify the target substance and then quantify its content. The other is utilizing reaction specificity to directly measure the amount of a specific substance in a complex sample. The process of purification-quantification is prone to result in loss of bioactivity and error, especially when the process is sophisticated and protracted. Thus assay techniques nowadays are mostly developed towards the specific reaction approach. The use of biosensor is one of the examples.
A biosensor typical consists of recognizable molecules, transducer and signal processor. The recognizable molecules are located on the surface of a sensing region of transducer to contact the target substance and react with it. Thus recognizable molecules must possess specificity for the target substance to enhance sensor selectivity. Commonly used recognizable molecules include biological tissue, microorganism, organelle, cell receptor, enzyme, antigen and antibody.
The function of a transducer is to convert changes in the physical quantity or chemical quantity of recognizable molecules after its reaction with the target substance into electronic signals. Physical quantity or chemical quantity could be optically, mass, thermochemically, electrochemically or magnetically. For example, in a biosensor system using enzyme as recognizable molecules, the reaction between enzyme and substrate is highly selective, and heat, changes in pH or absorption band, or other chemical substances would occur in the reaction process. Coupled with a proper transducer (e.g. thermocouple, electrode, photon counter, etc.), the changes in the process are converted into current signals, which are then read and process by a signal processor to determine the properties and content of the target substance. In the same way, when the quartz crystal microbalance (one kind of acoustics sensing elements) is used as a transducer, the binding of target substance to recognizable molecules coated on the surface of quartz crystal causes mass change on it, which leads to changes in the frequency of quartz crystal and allows measurement of the content of target substance. But to modify recognizable molecules on the surface of the sensing region of transducer usually need troublesome surface treatment and protein immobilization technics, and result in poor detection sensitivity and signal reproducibility. To render the use of highly sensitive acoustics sensor more efficient and free of restrictions, magnetic material modified with recognizable molecules is incorporated in the development of related techniques.
A prior art (U.S. Pat. No. 6,294,342) utilizes a magnetically responsive reagent that can recognize the target substance and a mobile solid phase reagent to determine the presence or amount of target substance contained in a sample by measuring the response to the magnetic field of the magnetically responsive reagent, or that of the mobile solid phase reagent. This prior art requires the combined use of magnetically responsive reagent and mobile solid phase reagent to produce measurable effect. Such effect is weight change caused by the changes in the attraction or repulsion between magnet and magnetic bead. Also, the method disclosed in the prior art is sensitive only to the level of microgram (μg).
Another prior art (U.S. Pat. No. 5,660,990) discloses the use of a capture agent to capture the target substance and then bind to a signal producing agent, and signals produced by the signal producing agent are detected and measured. In this technique, the use of additional agents adds more steps to the process and restrictive binding conditions tend to result in error. U.S. Pat. No. 6,342,396 discloses a method of immobilizing receptor on the surface of a capturing means to capture recognizable particles in a test sample. In this technique, the use of a specific receptor on the capturing means limits its application to specific analyte, or the surface of capturing means needs to be replaced for it to analyze other substances. Thus the technique lacks the value of general application.
This invention aims to provide a biosensor device and analytical method that are more sensitive, simpler and don't need use extra labeling materials.